The long-term objectives of this work are to use novel technologies to find better ways to diagnose and treat patients with antimalarial drug resistant parasites in India. Drug resistance is a tremendous threat to the treatment of patients, and in P. falciparum, resistance has arisen against all classes of first line anti-malaria drugs. Indeed, several have had to be withdrawn from use in many in countries. Surveillance for drug resistance is a significant challenge, because once enough treatment failures have aroused suspicions of resistance, the spread of resistance is likely to be well advanced. In this project, we propose to use new technologies, including next generation genomics, to study anti-malarial drug resistance in India. Specifically, we will: (1) use new generation sequencing technologies to detect evidence of the eariy signs of failure of ACT in P. falciparum and chloroquine in P. vivax;(2) Develop a non-genetic diagnostic test to identify drug resistance forms of Plasmodium parasites in natural infections;(3) Construct a genetic diversity map of P. vivax in India to determine linkage disequilibrium and provide preliminary data for a haplotype map that can be used for association studies of drug resistance. This project is part of a Center for the Study of Complex Malaria in India (CSCMi). The work, which will be a collaboration between Indian clinicians and epidemiologists, and US-based geneticists and evolutionary biologists, will develop next generation resistance management tools necessary for reducing the burden of both P. falciparum and P. vivax health burdens on the Indian subcontinent.